2-199919515-A-G

Variant names:

• chr2-199919515-A-G
• rs281787
• NM_153689.6:c.334-5547A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153689.6(C2orf69):​c.334-5547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,048 control chromosomes in the GnomAD database, including 35,845 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (35845 hom., cov: 31)
• Consequence: C2orf69 NM_153689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

Genes affected

C2orf69 (HGNC:26799): (chromosome 2 open reading frame 69) Involved in oxidative phosphorylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2orf69	NM_153689.6	c.334-5547A>G		intron_variant	Intron 1 of 1	ENST00000319974.6	NP_710156.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf69	ENST00000319974.6	c.334-5547A>G		intron_variant	Intron 1 of 1	1	NM_153689.6	ENSP00000312770.5
C2orf69	ENST00000491721.1	n.466+7744A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103803 AN: 151930 Hom.: 35791 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.683 AC: 103917 AN: 152048 Hom.: 35845 Cov.: 31 AF XY: 0.689 AC XY: 51225 AN XY: 74312

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.658

Alfa AF: 0.652 Hom.: 67113

Bravo AF: 0.687

Asia WGS AF: 0.811 AC: 2822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs281787; hg19: chr2-200784238;